chr9-35682350-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000378292.9(TPM2):c.773-187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 947,914 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 13 hom. )
Consequence
TPM2
ENST00000378292.9 intron
ENST00000378292.9 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.36
Genes affected
TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 9-35682350-G-A is Benign according to our data. Variant chr9-35682350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205261.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00435 (662/152296) while in subpopulation NFE AF= 0.00373 (254/68016). AF 95% confidence interval is 0.00336. There are 5 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 662 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM2 | NM_001301226.2 | c.773-187C>T | intron_variant | ||||
TPM2 | NM_213674.1 | c.773-187C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM2 | ENST00000378292.9 | c.773-187C>T | intron_variant | 1 | |||||
TPM2 | ENST00000644325.1 | c.*358C>T | 3_prime_UTR_variant | 4/4 | |||||
TPM2 | ENST00000329305.6 | c.773-187C>T | intron_variant | 2 | A1 | ||||
TPM2 | ENST00000643485.1 | n.1499C>T | non_coding_transcript_exon_variant | 8/8 |
Frequencies
GnomAD3 genomes AF: 0.00436 AC: 663AN: 152178Hom.: 5 Cov.: 32
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GnomAD4 exome AF: 0.00353 AC: 2812AN: 795618Hom.: 13 Cov.: 11 AF XY: 0.00327 AC XY: 1329AN XY: 406426
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GnomAD4 genome AF: 0.00435 AC: 662AN: 152296Hom.: 5 Cov.: 32 AF XY: 0.00567 AC XY: 422AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at